POS0608 PROGRESSIVE INCREASE IN THE DIAGNOSTIC DELAY AND PERSISTENTLY SEVERE CLINICAL PRESENTATION OVER THE YEARS IN AUTOANTIBODY-NEGATIVE PATIENTS WITH RHEUMATOID ARTHRITIS IN THE SETTING OF AN EARLY ARTHRITIS CLINIC
Authors: L. De Stefano, B. D’Onofrio, G. Sakellariou, A. Manzo, C. Montecucco, S. Bugatti
Journal: Annals of the Rheumatic Diseases (2022)

Background Over the past 20 years, despite the widespread diffusion of dedicated early arthritis clinics (EAC) and more sensitive classification criteria, the percentage of patients seen within the window of opportunity remains low, and the new RA criteria, heavily weighted on autoantibodies, may have further hindered the recognition and treatment of seronegative patients. Objectives we analysed changes in the diagnostic delay and clinical presentation of patients with RA admitted to the EAC of the Division of Rheumatology of the San Matteo University Hospital, Pavia, Italy, from its institution in 2005 to 2017. Methods Referral criteria to the EAC have remained stable over the years and include ≥3 swollen joints (SJs) or, in case of &lt;3 SJs, a positive squeeze test or morning stiffness &gt;30 min. From all early arthritis patients (n=1.553), we selected 668 patients fulfilling at enrolment at least the 1987 ACR criteria for RA before December 2010 (n=345, 88.4% also fulfilling 2010 criteria), and at least the 2010 ACR/EULAR criteria after January 2011 (n=323, 63.5% also fulfilling 1987 criteria). Time from first self-reported joint symptom to referral (diagnostic delay) was compared across different time periods: (i) 2005-2007; (ii) 2008-2010; (iii) 2011-2013; (iv) 2014-2017. Clinical characteristics were collected according to standardised assessments. Data were analysed in the total population and after stratification for the autoantibody status (double negative for rheumatoid factor, RF, and anti-citrullinated protein antibodies, ACPA vs RF and/or ACPA positive). Results In all, the diagnostic delay collectively increased from a mean (SD) of 20.8 (20.5) weeks before 2010 to 24.4 (20.6) weeks thereafter (p=0.02), and the proportion of patients diagnosed within 12 weeks non-significantly decreased from 39.3% to 35.3%. Still, patients presented with progressively milder inflammatory markers despite unchanged joint tenderness and patient-reported outcomes (PROs). Trends were, however, remarkably different in different autoantibody subgroups. In RF/ACPA-positive patients, a stable proportion of 41-44% was diagnosed within 12 weeks (Figure 1 A ). At presentation, patients had fewer SJs and lower C-reactive protein (CRP) levels; the mean decrease of SJs and CRP from 2005-2007 to 2014-2017 were -5.6 and -1.1 mg/dl, respectively (Figure 1 B ). The improvement in PROs was smaller but still significant over time (Figure 1 C ). In contrast, in autoantibody-negative patients, the proportion of patients diagnosed within 12 weeks progressively decreased from 37.9% to 25.6% (p=0.08) (Figure 1 D ). Furthermore, the improvement over time of inflammatory features, especially of SJs, was significant but smaller than autoantibody-patients, and PROs such as pain and global assessment of disease activity remained severely impacting with mean values of up 60 mm even in recent times (Figure 1 E,F ). Figure 1. Time to diagnosis and clinical presentation of autoantibody-positive and –negative patients with early rheumatoid arthritis. ( A , D ) Proportion of patients diagnosed within 12 weeks from symptoms’ onset among autoantibody-positive ( A ) and autoantibody-negative ( D ) rheumatoid arthritis (RA) in different time periods. ( B , C , E , F ) Values of swollen joints (SJC28), C-reactive protein (CRP) ( B , E ), and visual analogue scales (VAS) for pain and patient global assessment (PGA) of disease activity ( C , F ) in autoantibody-positive ( B , C ) and autoantibody-negative ( E , F ) RA in different time periods. Values are expressed as means and standard errors. Conclusion Collectively, our data indicate that a large proportion of patients with RA still lack early diagnosis despite dedicated early access to rheumatology care; from 2010 onwards, autoantibody-positive patients are diagnosed with a milder and less disabling disease, while autoantibody-negative patients are at increased risk of delayed diagnosis, and remain burdened with severe disease Disclosure of Interests Ludovico De Stefano Speakers bureau: Gilead, Bernardo D’Onofrio: None declared, Garifallia Sakellariou: None declared, Antonio Manzo: None declared, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Gilead, Pfizer, Roche, Sanofi, Serena Bugatti Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Gilead, Pfizer, Sanofi, Grant/research support from: Pfizer